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Study Evaluating the Safety and Efficacy of JCARH125 in Subjects With Relapsed and/or Refractory Multiple Myeloma (EVOLVE)

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ClinicalTrials.gov Identifier: NCT03430011
Recruitment Status : Recruiting
First Posted : February 12, 2018
Last Update Posted : October 12, 2018
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Juno Therapeutics, Inc.

Brief Summary:
This is an open-label, multicenter, Phase 1/2 study to determine the safety and efficacy of JCARH125, a CAR T-cell product that targets B-cell maturation antigen (BCMA), in adult subjects with relapsed and/or refractory multiple myeloma. The study will include a Phase 1 part to determine the recommended dose of JCARH125 in subjects with relapsed and/or refractory multiple myeloma, followed by a Phase 2 part to further evaluate the safety and efficacy of JCARH125 at the recommended dose.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Biological: JCARH125 Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 118 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Protocol H125001: An Open-Label Phase 1/2 Study of JCARH125, BCMA-targeted Chimeric Antigen Receptor (CAR) T Cells, in Subjects With Relapsed or Refractory Multiple Myeloma
Actual Study Start Date : February 1, 2018
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : March 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: JCARH125
Subjects will receive a course of lymphodepleting chemotherapy with fludarabine and cyclophosphamide followed by a single dose of JCARH125
Biological: JCARH125
Participants will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of JCARH125. During JCARH125 production, participants may receive bridging chemotherapy for disease control. Following successful generation of JCARH125 product, participants will receive a course of lymphodepleting chemotherapy followed by one dose of JCARH125 administered intravenously (IV).




Primary Outcome Measures :
  1. Phase 1: Incidence of dose-limiting toxicities (DLTs) [ Time Frame: 21 days ]
    Proportion of subjects with adverse events meeting DLT criteria

  2. Phase 1: Incidence and severity of adverse events [ Time Frame: 2 years ]
    Proportion of subjects with adverse events overall and by severity grade

  3. Phase 2: Overall response rate [ Time Frame: 2 years ]
    Proportion of subjects with a partial response or better by International Myeloma Working Group (IMWG) criteria


Secondary Outcome Measures :
  1. Phase 1 and Phase 2: Maximum concentration (Cmax) of JCARH125 in the blood [ Time Frame: 2 years ]
  2. Phase 1 and Phase 2: Time to maximum concentration (Tmax) of JCARH125 in the blood [ Time Frame: 2 years ]
  3. Phase 1 and Phase 2: Area under the concentration vs time curve (AUC) of JCARH125 in the blood [ Time Frame: 2 years ]
  4. Phase 1 and Phase 2: Complete response rate [ Time Frame: 2 years ]
    Proportion of subjects with a complete response by IMWG criteria

  5. Phase 1 and Phase 2: Depth of response [ Time Frame: 2 years ]
    Proportion of subjects who are negative for minimal residual disease (MRD)

  6. Phase 2: incidence and severity of adverse events [ Time Frame: 2 years ]
    Proportion of subjects with adverse events overall and by severity grade



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  1. Diagnosis of multiple myeloma (MM) with relapsed and/or refractory disease. Participants must have received at least 3 prior lines of therapy. Participants must have previously received all of the following therapies and must be refractory to the last line of therapy prior to entering the study:

    1. Autologous stem cell transplant
    2. A regimen that included an immunomodulatory agent (eg, thalidomide, lenalidomide, pomalidomide) and a proteasome inhibitor (eg, bortezomib, carfilzomib, ixazomib), either alone or in combination
    3. Anti-CD38 (eg, daratumumab) as part of a combination regimen or as a monotherapy

    Subjects who were not candidates to receive one or more of the above treatments (ie, contraindicated) are eligible.

  2. Subjects must have measurable disease.
  3. Subject must be willing to provide fresh bone marrow samples during Screening (and prior to study treatment, if required).
  4. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  5. Adequate renal, bone marrow, hepatic, pulmonary, and cardiac function

Exclusion Criteria:

  1. Subjects with known active or history of CNS involvement by malignancy
  2. Subjects with solitary plasmacytoma; active or history of plasma cell leukemia (PCL); Waldenstrom's macroglobulinemia; Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin changes (POEMS) syndrome; or symptomatic amyloidosis
  3. Subjects who are considered eligible to receive an autologous stem cell transplant
  4. History of another primary malignancy that has not been in remission for at least 2 years. The following are exempt from the 2-year limit: non-melanoma skin cancer, completely resected Stage 1 solid tumor with low risk for recurrence, curatively treated localized prostate cancer, cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on Pap smear, and in situ breast cancer that has been completely resected.
  5. Require systemic immunosuppressive therapies (eg, calcineurin inhibitors, methotrexate, mycophenolate, rapamycin, thalidomide, immunosuppressive antibodies such as anti-IL-6 or anti-IL-6 receptor [IL-6R])
  6. Prior CAR T-cell or other genetically-modified T-cell therapy
  7. Prior treatment with a BCMA-targeted agent
  8. Prior allogeneic stem cell transplant
  9. History or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03430011


Contacts
Contact: Juno Medical Information 866-599-JUNO (5866) medicalinformation@junotherapeutics.com

Locations
United States, Alabama
University of Alabama Recruiting
Birmingham, Alabama, United States, 35294
Contact: Tiffany D Hill, RN, BSN    205-996-8023    tiffanydhill@uabmc.edu   
Principal Investigator: Luciano Costa, MD, PhD         
United States, California
City of Hope Comprehensive Cancer Center Recruiting
Duarte, California, United States, 91010
Contact: Myo Htut, MD    626-218-2405 ext 82405    mhtut@coh.org   
Principal Investigator: Myo Htut, MD         
University of California Recruiting
San Francisco, California, United States, 94143
Contact: Helen Diller Family Comprehensive Cancer Center       HDFCCC.CIP@ucsf.edu   
Principal Investigator: Sandy Wong, MD         
United States, Georgia
Winship Cancer Institute at Emory University Not yet recruiting
Atlanta, Georgia, United States, 30322
Contact: Jonathan Kaufman, MD    404-778-1900    jlkaufm@emory.edu   
Principal Investigator: Jonathan Kaufman, MD         
United States, Illinois
The University of Chicago Medicine Recruiting
Chicago, Illinois, United States, 60637
Contact: Rebecca Malloy    773-834-1475    rmalloy@medicine.bsd.uchicago.edu   
Principal Investigator: Andrzej Jakubowiak, MD, PhD         
United States, New Jersey
Hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Leah Cappadona, RN    551-996-5078    Leah.Cappadona@hackensackmeridian.org   
Principal Investigator: David Siegel, MD, PhD         
United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14203
Contact: Lisa Martin    716-845-4892    Lisa.Martin@RoswellPark.org   
Contact: Aaron Pry    716-845-2910    Aaron.Pry@RoswellPark.org   
Principal Investigator: Kelvin Lee, MD         
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Claudia Diamonte, RN    212-639-5317    diamontc@mskcc.org   
Principal Investigator: Sham Mailankody, MD         
United States, Washington
Swedish Cancer Institute Recruiting
Seattle, Washington, United States, 98104
Contact: Tenzin Tsomo    206-386-2831    Tenzin.Tsomo@swedish.org   
Principal Investigator: William Bensinger, MD         
Sponsors and Collaborators
Juno Therapeutics, Inc.
Celgene Corporation
Investigators
Study Director: John Byon, MD, PhD Juno Therapeutics, Inc.

Responsible Party: Juno Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03430011     History of Changes
Other Study ID Numbers: H125001
First Posted: February 12, 2018    Key Record Dates
Last Update Posted: October 12, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Juno Therapeutics, Inc.:
JCARH125
chimeric antigen receptor
multiple myeloma
CAR T cells
B-cell maturation antigen
BCMA
autologous T-cell therapy
immunotherapy

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases